rs200515246
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_024537.4(CARS2):c.870C>T(p.Cys290=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
CARS2
NM_024537.4 synonymous
NM_024537.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.574
Genes affected
CARS2 (HGNC:25695): (cysteinyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of cysteine to tRNA molecules. A splice-site mutation in this gene has been associated with a novel progressive myoclonic epilepsy disease with similar symptoms to MERRF syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 13-110667389-G-A is Benign according to our data. Variant chr13-110667389-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475636.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.574 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000394 (6/152290) while in subpopulation EAS AF= 0.000771 (4/5190). AF 95% confidence interval is 0.000263. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.870C>T | p.Cys290= | synonymous_variant | 8/15 | ENST00000257347.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.870C>T | p.Cys290= | synonymous_variant | 8/15 | 1 | NM_024537.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251314Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135850
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GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461154Hom.: 0 Cov.: 29 AF XY: 0.0000234 AC XY: 17AN XY: 726910
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation defect type 27 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at